Ю.О. Митропольський — вчений та вихователь молоді

Висвітлено наукову діяльність та роботу з підготовки наукових кадрів академіка Ю.О. Митропольського. Змальовано його риси як вченого та вихователя молоді.Освещены научная деятельность и работа по подготовке научных кадров академика Ю.А.Митропольского. Обрисованы его черты как ученого и воспитателя молодежи.The paper highlights research and tutorial activities by Academician Yu.O. Mitropolsky. His qualities as a scientist and a tutor of youth are outlined

Minimally important change determined by a visual method integrating an anchor-based and a distribution-based approach

Background: Minimally important changes (MIC) in scores help interpret results from health status instruments. Various distribution-based and anchor-based approaches have been proposed to assess MIC. Objectives: To describe and apply a visual method, called the anchor-based MIC distribution method, which integrates both approaches. Method: Using an anchor, patients are categorized as persons with an important improvement, an important deterioration, or without important change. For these three groups the distribution of the change scores on the health status instrument are depicted in a graph. We present two cut-off points for an MIC: the ROC cut-off point and the 95% limit cut-off point. Results: We illustrate our anchor-based MIC distribution method determining the MIC for the Pain Intensity Numerical Rating Scale in patients with low back pain, using two conceivable definitions of minimal important change on the anchor. The graph shows the distribution of the scores of the health status instrument for the relevant categories on the anchor, and also the consequences of choosing the ROC cut-off point or the 95% limit cut-off point. Discussion: The anchor-based MIC distribution method provides a general framework, applicable to all kind of anchors. This method forces researchers to choose and justify their choice of an appropriate anchor and to define minimal importance on that anchor. The MIC is not an invariable characteristic of a measurement instrument, but may depend, among other things, on the perspective from which minimal importance is considered and the baseline values on the measurement instrument under study. A balance needs to be struck between the practicality of a single MIC value and the validity of a range of MIC values. © 2006 Springer Science+Business Media B.V

Pancreatico-portal dissociation: A canine model to evaluate the hepatic maintenance effects of partial portal flow diversion and pancreatic hormone deprivation

Pancreatico-portal dissociation provides a viable canine experimental model for evaluating the effects of portal flow reduction and pancreatic hormone deprivation in liver mainenance. Initial studies indicate flow as a "vehicle" for substrate (and/or hormone) delivery and imply a possible contribution to hepatic maintenance of the gastrosplenic venous axis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23638/1/0000602.pd

Male-female differences in thoracic aortic diameters at presentation of acute type A aortic dissection

Background: Acute type A aortic dissection (ATAAD) is a highly lethal event, associated with aortic dilatation. It is not well known if patient height, weight or sex impact the thoracic aortic diameter (TAA) at ATAAD. The study aim was to identify male–female differences in TAA at ATAAD presentation. Methods: This retrospective cross-sectional study analysed all adult patients who presented with ATAAD between 2007 and 2017 in two tertiary care centres and underwent contrast enhanced computed tomography (CTA) before surgery. Absolute aortic diameters were measured at the sinus of Valsalva (SoV), ascending (AA) and descending thoracic aorta (DA) using double oblique reconstruction, and indexed for body surface area (ASI) and height (AHI). Z-scores were calculated using the Campens formula. Results: In total, 59 % (181/308) of ATAAD patients had CT-scans eligible for measurements, with 82 female and 99 male patients. Females were significantly older than males (65.5 ± 12.4 years versus 60.3 ± 2.3, p = 0.024). Female patients had larger absolute AA diameters than male patients (51.0 mm [47.0–57.0] versus 49.0 mm [45.0–53.0], p = 0.023), and larger ASI and AHI at all three levels. Z-scores for the SoV and AA were significantly higher for female patients (2.99 ± 1.66 versus 1.34 ± 1.77, p &lt; 0.001 and 5.27 [4.38–6.26] versus 4.06 [3.14–5.02], p &lt; 0.001). After adjustment for important clinical factors, female sex remained associated with greater maximal TAA (p = 0.019). Conclusion: Female ATAAD patients had larger absolute ascending aortic diameters than males, implying a distinct timing in disease presentation or selection bias. Translational studies on the aortic wall and studies on growth patterns should further elucidate these sex differences.</p

Melphalan 140mg/m2 or 200mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party

Melphalan at a dose of 200mg/m2 is standard conditioning prior to autologous haematopoietic stem cell transplantation for multiple myeloma, but a dose of 140mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine if melphalan 200 and melphalan 140 are equally effective and tolerable in clinically relevant patient subgroups we analysed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, haematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 (n=245) and melphalan 200 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 versus melphalan 140: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favoured melphalan 140 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 and melphalan 140 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favour melphalan 200 or melphalan 140 for key transplant outcomes (NCT01362972)

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Allergen immunotherapy for IgE-mediated food allergy : a systematic review and meta-analysis

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. Methods: We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. Results: We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the robustness of summary estimates of effectiveness and safety of AIT for food allergy. None of the studies reported data on health economic analyses. Conclusions: AIT may be effective in raising the threshold of reactivity to a range of foods in children with IgE-mediated food allergy whilst receiving (i.e. desensitization) and post-discontinuation of AIT. It is, however, associated with a modest increased risk in serious systemic adverse reactions and a substantial increase in minor local adverse reactions. More data are needed in relation to adults, long term effects, the impact on QoL and the cost-effectiveness of AIT.Peer reviewe

Antipsychotic drug use and community-acquired pneumonia

Antipsychotics are generally distinguished as atypical and typical agents, which are indicated in the treatment of acute and chronic psychoses and other psy

Rating the methodological quality in systematic reviews of studies on measurement properties: a scoring system for the COSMIN checklist

Background: The COSMIN checklist is a standardized tool for assessing the methodological quality of studies on measurement properties. It contains 9 boxes, each dealing with one measurement property, with 5-18 items per box about design aspects and statistical methods. Our aim was to develop a scoring system for the COSMIN checklist to calculate quality scores per measurement property when using the checklist in systematic reviews of measurement properties. Methods: The scoring system was developed based on discussions among experts and testing of the scoring system on 46 articles from a systematic review. Four response options were defined for each COSMIN item (excellent, good, fair, and poor). A quality score per measurement property is obtained by taking the lowest rating of any item in a box ("worst score counts"). Results: Specific criteria for excellent, good, fair, and poor quality for each COSMIN item are described. In defining the criteria, the "worst score counts" algorithm was taken into consideration. This means that only fatal flaws were defined as poor quality. The scores of the 46 articles show how the scoring system can be used to provide an overview of the methodological quality of studies included in a systematic review of measurement properties. Conclusions: Based on experience in testing this scoring system on 46 articles, the COSMIN checklist with the proposed scoring system seems to be a useful tool for assessing the methodological quality of studies included in systematic reviews of measurement properties. © The Author(s) 2011

Hospital physicians' and older patients' agreement with individualised STOPP/START-based medication optimisation recommendations in a clinical trial setting

OBJECTIVE: To evaluate the agreement of hospital physicians and older patients with individualised STOPP/START-based medication optimisation recommendations from a pharmacotherapy team. METHODS: This study was embedded within a large European, multicentre, cluster randomised controlled trial examining the effect of a structured medication review on drug-related hospital admissions in multimorbid (≥ 3 chronic conditions) older people (≥ 70 years) with polypharmacy (≥ 5 chronic medications), called OPERAM. Data from the Dutch intervention arm of this trial were used for this study. Medication review was performed jointly by a physician and pharmacist (i.e. pharmacotherapy team) supported by a Clinical Decision Support System with integrated STOPP/START criteria. Individualised STOPP/START-based medication optimisation recommendations were discussed with patients and attending hospital physicians. RESULTS: 139 patients were included, mean (SD) age 78.3 (5.1) years, 47% male and median (IQR) number of medications at admission 11 (9-14). In total, 371 recommendations were discussed with patients and physicians, overall agreement was 61.6% for STOPP and 60.7% for START recommendations. Highest agreement was found for initiation of osteoporosis agents and discontinuation of proton pump inhibitors (both 74%). Factors associated with higher agreement in multivariate analysis were: female gender (+ 17.1% [3.7; 30.4]), ≥ 1 falls in the past year (+ 15.0% [1.5; 28.5]) and renal impairment i.e. eGFR 30-50 ml/min/1.73 m2; (+ 18.0% [2.0; 34.0]). The main reason for disagreement (40%) was patients' reluctance to discontinue or initiate medication. CONCLUSION: Better patient and physician education regarding the benefit/risk balance of pharmacotherapy, in addition to more precise and up-to-date medical records to avoid irrelevant recommendations, will likely result in higher adherence with future pharmacotherapy optimisation recommendations. CLINICAL TRIAL REGISTRATION: Trial Registration Number NCT02986425